Mapping the transcriptomic cosmos of
inflammatory bowel disease

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Single-cell analysis of IBD tissues at a population scale

We generated the largest single-cell datasets of inflammatory bowel disease relevant samples, spanning millions of cells across the ileum, blood and rectum, from hundreds of individuals with and without inflammatory bowel disease. We were able to perform well-powered analyses comparing the effects of disease, location and genetics on cellular expression.

Transcriptomic consequences of ileal inflammation

Cell type mapping and gene expression insights from the terminal ileum, including genes dysregulated in active Crohn's and enrichment of GWAS signal in particular cell types.

Blood and gut immune comparison

Paired analysis of immune cells in blood and gut, revealing tissue-specific changes.

sc-eQTLs to unlock GWAS
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Joint atlas of gut and blood, identifying eQTLs and linking genetic risk to cell types and effector genes.

Future studies
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Read about how we are building upon this work to answer other questions about IBD biology

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Transcriptomic consequences of ileal inflammation

Comprehensive profiling of terminal ileum cell types, highlighting cell types present in the termninal ileum, key differences between inflamed  and uninflamed bowels and which cell types are enriched for dysruptive genetic variants.

Krzak, Alegbe, Taylor, Jones et al.

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Blood and gut immune  comparison

Identification and quantification of the differences in immune cells between blood and gut samples from individuals with Crohn's disease. Several populations and processes are seen to be enriched in either tissue and blood.

Ramirez-Navarro et al.

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sc-eQTLs to unlock GWAS

Identification of eQTLs within single-cell resolved cell types from ileum, rectum and blood. Integrating these eQTLs with exist disease risk GWAS offers insight into the genes and cell types causally driving inflammatory bowel disease.

Alegbe, Harris et al.

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Future studies

Building on the foundations that this work has laid down we intend to take further steps to use single-cell RNA-sequencing approaches to better understand IBD biology. These include:
IBDresponse
OpenIBD
Long-read sequencing IBDverse

For patients, friends and family

Get straightforward answers about our datasets, publications, and findings. Designed for those who have or know someone who has an inflammatory bowel disease such as Crohn's disease or ulcerative colitis.

What do these results mean for me?

Whilst the results of our study are promising we emphasise caution in their interpretation.

Any proposed novel therapeutic targets can take many years of validation and trials before they can reach the clinic but our research is one step closer to that goal.

What did you discover?

We have released three manuscripts detailing our findings for the wider scientific and medical community to read. These manuscripts are not written with the public in mind and can contain highly technical terminology so we have also written a short summary of these findings which can be found here.

Can I access my data?

All patient information is confidential so before sharing any data, we carefully removed any information that could identify individual participants.

However we want to make sure that the information collected and generated as part of this project can be used by other researchers to increase our understanding of inflammatory bowel disease and improve the treatment of people living with it. To support this goal, we have made these data available for others to use.  Some data will be freely available to download directly from this website. More detailed datasets, including the clinical information gathered during this project, will be require review by a data access committee to ensure that the data are used responsibly.

Who paid for this project?

The project was funded by:

  • Crohn's and Colitis Foundation, a charity dedicated to supporting people with and funding research into inflammatory bowel diseases
  • The Wellcome Trust, a charity which supports many forms of biomedical research primarily in the UK and provides core funding for the Wellcome Sanger Institute
  • Open Targets, a collaboration between academia and pharmaceutical partners seeking to develop new treatments for inflammatory bowel diseases

Can I ask a member of the team about this work?

Yes. A contact email address for the authors of these studies is provided at the bottom of this page. Please note that these questions should only be related to this work rather than IBD in general.

How can I get help with my IBD?

We are primarily research scientists and cannot offer medical advice into the treatment of IBD. You should contact your doctor if you have issues with your disease.

Explore the IBDverse

Here we present the IBDverse data from each of our three papers in both an interactive and downloadable format, allowing IBD researchers the opportunity to conduct their own focused analyses.

Krzak, Alegbe, Taylor, Jones et al.
Ramirez-Navarro et al.
Alegbe, Harris et al.
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Terminal ileum single-cell analyses in health and disease

Single-cell RNA-sequencing data and results from 111 CD patients and 232 healthy controls

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DGE: CD [inflamed] vs healthy
DGE: CD [uninflamed] vs healthy
DGE: CD [inflammation severity]
DGE: Age
DGE: Sex
DGE: Organoid [stim.] vs organoid [unstim.]
DGE: Organoid [CD unstim.] vs organoid [healthy unstim.]
Heritability partitioning
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CellxGene browser (atlas anndata)

Download data

Atlasing anndata (70 samples)
Analysis anndata (343 samples)
Organoid anndata (14 samples)
Individual metadata (343 individuals)
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Authors

Research led by Monika Krzak, Tobi Alegbe, Leland Taylor and Gareth-Rhys Jones with contributions from a multidisciplinary team under the direction of senior investigators Carl Anderson and Tim Raine.
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Paired immune cell profiling between the intestine and blood

Comparison of immune cell populations between blood and terminal ileum from the 125 individuals with Crohn's disease.

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DGE: Blood vs TI [available upon publication]
DGE: Inflammation [available upon publication]
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Explore data

CellxGene browser (atlas anndata) [available upon publication]

Download data

Atlas anndata [available upon publication]
Analysis anndata [available upon publication]
Individual metadata [available upon publication]
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Authors

Research led by Lucia Ramirez-Navarro with contributions from a multidisciplinary team under the direction of senior investigators Tim Raine and Carl Anderson.
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eQTL mapping across IBD-relevant tissues

Joint single-cell eQTL analysis across terminal ileum, rectum, and blood in over 732 samples from 421 individuals.

Download results

TI eQTLs [available upon publication]
Rectal eQTLs [available upon publication]
Blood eQTLs [available upon publication]
Cross-tissue eQTLs [available upon publication]
Interaction eQTLs [available upon publication]
IBD colocalisations [available upon publication]
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Explore the data

CellxGene browser (atlas anndata) [available upon publication]
eQTL visualiser [available upon publication]

Download data

Atlas anndata [available upon publication]
Analysis anndata [available upon publication]
Genotype array data [available upon publication]
Individual metadata [available upon publication]
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Authors

Research led by Tobi Alegbe and Bradley Harris with contributions from a multidisciplinary team under the direction of senior investigators Carl Anderson and Tim Raine.

Team

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Carl Anderson
Co-senior investigator
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Tim Raine
Co-senior investigator
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Bradley Harris
Postdoctoral fellow
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Cristina Cotobal Martin
Senior Staff Scientist
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Gareth-Rhys Jones
Clinical fellow
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Leland Taylor
Postdoctoral fellow
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Lucia Ramirez-Navarro
Predoctoral fellow
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Monika Krzak
Postdoctoral fellow
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Rebecca McIntyre
Principal Staff Scientist
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Tobi Alegbe
Predoctoral fellow

Clinical team

Our clinical team in the department of gastroenterology at Addenbrooke's hospital collected pinch biopsies during routine endoscopic procedures and sent them via courier for sequencing at the Wellcome Sanger Institute.
It consisted of Claire Dawson, Tina Thompson, Kenneth Arestang, Wendy Garri, Biljana Brezina, Charry Queen Caballes, Nilanga Nishad and Miles Parkes.

Laboratory team

Our laboratory team within the Anderson Lab at the Wellcome Sanger Institute developed a novel protocol for the processing of gastrointestinal biopsies in a gentle manner. They applied this protocol to over 600 IBDverse biopsies (together with processing over 100 blood samples) in order to curate the high quality single-cell datasets.
Under the leadership of Rebecca McIntyre and Cristina Cotobal Martin, it consisted of Mennatallah Ghouraba, Michelle Strickland, Noor Wana, May Xueqi Hu, Jason Skelton, Tong Deng, Jasmin Ostermayer and Kimberly Ai Xian Cheam.

Computational team

Once the data was generated, many individuals in the Anderson group at the Wellcome Sanger Institute performed quality control and data analysis to produce the processed datasets and arrive at the conclusions presented in our manuscripts.
It consisted of Monika Krzak, Tobi Alegbe, Leland Taylor, Lucia Ramirez-Navarro, Bradley Harris, Moritz Przybilla, Marcus Tutert, Ciro Ramirez Suastegui, Hanna Najgebauer, Saniya Khoullar and Eleonora Khabirova.

Collaborators

Outside of the above working teams we were fortunate enough to collaborate with many individuals, both internal and external, who were crucial to our research effort. This included Velislava Petrova, Carla Jones Bell, Nikolaos Panousis, Matiss Ozols, Guillaume Noell, Steven Leonard, Reem Satti, Daniele Corridoni, Vivek Iyer, David Ochoa and Chris Wallace.

Funders and partners
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Wellcome Trust
Open Targets
Crohn's and Colitis Foundation
University of
Cambridge
Addenbrooke's
Hospital
Wellcome
Sanger Institute